From the Guidelines
In TTP, therapeutic Plasma Exchange (PEX) is initiated according to existing guidelines, particularly in cases with life-threatening consequences, and is often combined with immunosuppressive medications. The process involves removing autoantibodies that target ADAMTS13, a crucial enzyme that prevents abnormal blood clotting, and replacing the plasma with donor plasma that contains functional ADAMTS13 1.
Key Points:
- PEX is recommended for patients with life-threatening consequences, such as CNS hemorrhage or thrombosis, or renal failure, as outlined in the guidelines for managing immune-related adverse events in patients treated with immune checkpoint inhibitor therapy 1.
- The treatment typically involves administering methylprednisolone 1 g IV daily for 3 days, with the first dose administered immediately after the first PEX, and may include rituximab and caplacizumab in certain cases 1.
- PEX should be continued until clinical progress is observed, and the decision to discontinue or modify treatment is based on the patient's response, including platelet count normalization and clinical improvement 1.
- The guidelines emphasize the importance of considering the risks and benefits of restarting immune checkpoint inhibitor therapy after an episode of TTP, and currently, there are no data to recommend restarting therapy in patients who have experienced TTP 1.
From the Research
How Plex Works in TTP
- Plex, or plasma exchange, is a crucial treatment for thrombotic thrombocytopenic purpura (TTP) 2, 3, 4, 5, 6.
- The process involves removing the patient's plasma, which contains autoantibodies against ADAMTS13, and replacing it with fresh frozen plasma (FFP) that contains functional ADAMTS13 3, 4, 5.
- Daily plasma exchange is typically performed, with the goal of replacing 1-1.5 times the patient's plasma volume with FFP 2, 3, 5.
- The treatment is usually continued until the patient's platelet count recovers and serum lactate dehydrogenase (LDH) levels normalize 2, 6.
- Plasma exchange can be performed using a variety of techniques, including centrifugal separation or membrane filtration 3.
Mechanism of Action
- The removal of autoantibodies against ADAMTS13 and the replacement with functional ADAMTS13 are thought to be the primary mechanisms by which plasma exchange works in TTP 3, 4, 5.
- ADAMTS13 is a von Willebrand factor-cleaving protease that helps to regulate the formation of blood clots 4, 5.
- In TTP, a severe deficiency of ADAMTS13 leads to the formation of microvascular platelet-rich thrombi, which can cause organ ischemia and other complications 4, 5.
Efficacy and Safety
- Plasma exchange has been shown to be highly effective in treating TTP, with response rates ranging from 80-90% 2, 3, 6.
- The treatment is generally well-tolerated, but can be associated with adverse events such as central venous catheter-related complications and transfusion-related acute lung injury (TRALI) 3, 5.
- The use of solvent-detergent treated plasma instead of FFP may help to reduce the risk of plasma-related side effects, but this has not been established by controlled clinical studies 3.